Slide 9:

Pharmacokinetics-1:

Pharmacokinetics-1 Nasal application results in peak levels of approximately 100 ng/mL in about 50 to 60 minutes. Smoking crack cocaine results in peak levels of 200 to 400 ng/mL in about 5 to 10 minutes

Pharmacokinetics-1:

Pharmacokinetics-1 Lipophilic – cross blood-brain-barrier Short half life – 60 min Very little cocaine is excreted unchanged in urine. So, unchanged cocaine in urine –drug used recently Screening is for cocaine metabolites in urine Main metabolites: Benzoylecgonine Ecgonine methyl ester In the presense of alcohol ….

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…. Cocaethylene Similar pharmacological properties. half-life about three times that of cocaine. low cocaine blood levels but significant toxic symptoms. More pentration to the blood–brain - greater high much more mortality and morbidity

Clinical toxicity-1:

Clinical toxicity-1 intense euphoria, but also agitation, seizures, and occasional cardiovascular accidents (strokes). It increases mental awareness and alertness with an associated feeling of well-being and euphoria. Fatigue is decreased and motor activity is increased, but coordination decreases at the same time. Profound physical and emotional depression, after prolonged use of cocaine.

Clinical toxicity-2:

Clinical toxicity-2 Cardiac effects are common, including tachycardia and other arrhythmias, hypertension, and myocardial ischemia or infarction. Other effects, such as sweating and hyperthermia, are often noted. The toxic dose of cocaine is estimated to equal 2 mg/kg body weight. Many deaths have resulted from cocaine abuse. When fatalities occur the immediate cause is usually intracranial hemorrhage, arrythmia,myocardial infarction, seizures, and/or trauma

Clinical toxicity-3:

Clinical toxicity-3 Ulceration of the nasal septum is always recorded as a complication of long-term nasal abuse of cocaine but this is, in fact, a rare phenomenon. Addictive after only few exposures Withdrawal reported – not severe as opiates Tolerance

Therapeutic uses:

Therapeutic uses Historically, local anesthetic in eye and ENT. now predominantly used for nasal and lacrimal duct surgery. The only local anesthetic causing vasoconstriction. The major disadvantages intense vasoconstrictor activity potential for cardiovascular toxicity. largely replaced synthetic local anesthetics . If vasoconstriction is desired for a procedure ,the anesthetic is combined with a vasoconstrictor such as phenylephrine or epinephrine.